SUMMARY Recent identification of TMEM184A as a heparin receptor in vascular cells provides an opportunity to investigate further the mechanism(s) by which the heparin receptor works in vivo. Saturating the heparin receptor decreases vascular smooth muscle cell proliferation and decreases inflammatory responses and angiogenesis in endothelial cells, while decreasing the receptor expression also decreases angiogenesis. The current proposal is designed to expand our knowledge about the heparin receptor and its function in both vascular smooth muscle cells and endothelial cells using a combination of cell culture assays, assays of developmental and regenerative angiogenesis in zebrafish, and employing a null mutant for the heparin receptor currently being developed. Specifically, we will test the hypothesis that the heparin receptor modulates growth factor and adhesion signaling in vascular smooth muscle cells through eNOS activation, examine the hypothesis that mechanotransduction through the endothelial flow mechanosensing complex involves TMEM184A, and test the hypothesis that the heparin receptor collaborates in signaling through the VEGFR2 pathway. Together these studies will provide data to confirm the mechanism(s) by which the heparin receptor is functioning and should yield clues to designing treatments for various vascular diseases that take advance of this modulatory system.